Staphylococcus aureus is the leading cause of hospital-acquired infections. The enzyme sortase A, present on the cell surface of S. aureus, plays a key role in bacterial virulence without affecting the bacterial viability. Inhibition of sortase A activity offers a powerful but clinically less explored therapeutic strategy, as it offers the possibility of not inducing any selective pressure on the bacteria to evolve drug-resistant strains. In this Perspective, we offer a chemical space narrative for the design of sortase A inhibitors, as delineated into three broad domains: peptidomimetics, natural products, and synthetic small molecules. This provides immense opportunities for medicinal chemists to alleviate the ever-growing crisis of antibiotic resistance.

中文翻译：

---

Sortase A 抑制的化学生物学：通往抗感染治疗剂的途径

金黄色葡萄球菌是医院获得性感染的主要原因。存在于金黄色葡萄球菌细胞表面的分选酶 A在不影响细菌活力的情况下在细菌毒力中起关键作用。抑制分选酶 A 活性提供了一种强大但在临床上探索较少的治疗策略，因为它提供了不诱导细菌产生任何选择压力以进化出耐药菌株的可能性。在这个视角中，我们为分选酶 A 抑制剂的设计提供了化学空间叙述，分为三个广泛的领域：肽模拟物、天然产物和合成小分子。这为药物化学家提供了巨大的机会来缓解日益严重的抗生素耐药性危机。